Phase 2a: Evaluate the annualized change in glomerular filtration rate (GFR) in subjects with ADPKD when treated with KD019

Original Primary Outcome Measures ICMJE (submitted: March 19, 2012)

Plasma pharmacokinetics of KD019 when administered to subjects with ADPKD [ Time Frame: an expected average of approximately 8 months ] [ Designated as safety issue: No ]

Measuring Peak plasma concentration (Cmax)

Documentation of the number and type of adverse events related to KD019 when administered to subjects with ADPKD [ Time Frame: an expected average of approximately 8 months ] [ Designated as safety issue: Yes ]

Plasma pharmacokinetics of KD019 when administered to subjects with ADPKD [ Time Frame: an expected average of approximately 8 months ] [ Designated as safety issue: No ]

Measuring time to maximum concentration (Tmax)

Plasma pharmacokinetics of KD019 when administered to subjects with ADPKD [ Time Frame: an expected average of approximately 8 months ] [ Designated as safety issue: No ]

Measuring drug clearance (CL)

Plasma pharmacokinetics of KD019 when administered to subjects with ADPKD [ Time Frame: an expected average of approximately 8 months ] [ Designated as safety issue: No ]

Measuring the area under the curve (AUC)

Plasma pharmacokinetics of KD019 when administered to subjects with ADPKD [ Time Frame: an expected average of approximately 8 months ] [ Designated as safety issue: No ]

Evaluate the safety profile, tolerability, and pharmacokinetics in subjects with ADPKD treated with KD019 on an alternative dosing schedule. Documentation of the number and type of adverse events related to KD019 when administered to subjects with ADPKD.

Original Secondary Outcome Measures ICMJE (submitted: March 19, 2012)

Exploratory measures of efficacy will be performed. [ Time Frame: an expected average of approximately 8 months ] [ Designated as safety issue: No ]

The primary objective of this study is to determine the safety, plasma pharmacokinetics, and maximum tolerated dose (MTD) of KD019 when administered to subjects with ADPKD.

Detailed Description

Phase 1:

Primary purpose is to determine the safety of KD019.

Dosing is for 28 days daily. After the 28-day treatment period, subjects will, at the discretion of the investigator, continue to receive study treatment for 24 months from their first dose or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the subject, or investigator decision. Subjects may continue beyond 24 months at the discretion of the investigator after consultation with the medical monitor.

All participants receive active KD019 study drug.

KD019 is an oral once daily tablet. Tablets are 50 mg, 100 mg and 150 mg in strength. Participants will enroll into three sequential dosing cohort levels (50 mg, 100 mg and 150 mg.). Participants in Phase 1b will have their dose increased or decreased to the MTD.

Study participants will have MRI of the abdomen (kidneys) at Screening and 6 months thereafter to explore effects of KD019.

Echocardiogram will be performed at Screening, Day 28, months 3 and 6 and every 6 months thereafter.

Phase 2:

Primary purpose is to compare the annualized change in glomerular filtration rate (GFR) in subjects with ADPKD when treated with KD019.

Two alternate dosing schedules will be explored to determine if they are more tolerable than daily dosing when used chronically in subjects with ADPKD.

KD019 will be either dosed on Monday, Wednesday and Friday of each week or Monday and Thursday of each week. Subjects will receive study treatment for 24 months from their first dose or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the subject, or investigator decision. Subjects may continue beyond 24 months at the discretion of the investigator after consultation with the sponsor.

All participants receive active KD019 study drug.

KD019 is an oral tablet dosed on Monday, Wednesday and Friday or Monday and Thursday of every week. Tablets are 50 mg, 100 mg, and 150 mg in strength.

Study participants will have MRI of the abdomen (kidneys) at Screening and Month 6 visit and every 6 months after to explore effects of KD019.

Echocardiogram will be performed at Screening, Day 28, and Months 3 and 6 and 6 months thereafter.

Study Type ICMJE

Interventional

Study Phase

Phase 1Phase 2

Study Design ICMJE

Allocation: Non-RandomizedIntervention Model: Single Group AssignmentMasking: Open LabelPrimary Purpose: Treatment

Condition ICMJE

Polycystic Kidney, Autosomal Dominant

Intervention ICMJE

Drug: KD019

Other Name: XL647

Study Arm (s)

Experimental: Cohort 1

One 50mg KD019 tablet per day for 28 days and up to 24 months

Intervention: Drug: KD019

Experimental: Cohort 2

Two 50mg KD019 tablets per day for 28 days and up to 24 months

Intervention: Drug: KD019

Experimental: Cohort 3

Three 50mg KD019 tablets per day for 28 days and up to 24 months

Intervention: Drug: KD019

Experimental: Phase 2a Monday, Wednesday, Friday

An alternate KD019 dosing schedule of dosing on Monday, Wednesday and Friday of each week for 24 months from their first dose or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the subject, or investigator decision

Intervention: Drug: KD019

Experimental: Phase 2a Monday and Thursday

An alternate KD019 dosing schedule of dosing on Monday and Thursday of each week for 24 months from their first dose or until the development of unacceptable toxicity, noncompliance, or withdrawal of consent by the subject, or investigator decision

Intervention: Drug: KD019

Experimental: Phase 2a, 50mg

One 50mg KD019 tablet per day for 28 days and up to 24 months

Intervention: Drug: KD019

Publications *

Not Provided

* Includes publications given by the data provider as well as publications
identified by ClinicalTrials.gov Identifier (NCT Number) in Medline.